Cancers, Vol. 16, Pages 1525: Dichloroacetate and Quercetin Prevent Cell Proliferation, Induce Cell Death and Slow Tumor Growth in a Mouse Model of HPV-Positive Head and Neck Cancer
Cancers, Vol. 16, Pages 1525: Dichloroacetate and Quercetin Prevent Cell Proliferation, Induce Cell Death and Slow Tumor Growth in a Mouse Model of HPV-Positive Head and Neck Cancer
Cancers doi: 10.3390/cancers16081525
Authors:
Yongxian Zhuang
Joseph D. Coppock
Allison B. Haugrud
John H. Lee
Shanta M. Messerli
W. Keith Miskimins
Elevated glucose uptake and production of lactate are common features of cancer cells. Among many tumor-promoting effects, lactate inhibits immune responses and is positively correlated with radioresistance. Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase that decreases lactate production. Quercetin is a flavonoid compound found in fruits and vegetables that inhibits glucose uptake and lactate export. We investigated the potential role and mechanisms of DCA, quercetin, and their combination, in the treatment of HPV-positive head and neck squamous cell carcinoma, an antigenic cancer subtype in need of efficacious adjuvant therapies. C57Bl/6-derived mouse oropharyngeal epithelial cells, a previously developed mouse model that was retrovirally transduced with HPV type-16 E6/E7 and activated Ras, were used to assess these compounds. Both DCA and quercetin inhibited colony formation and reduced cell viability, which were associated with mTOR inhibition and increased apoptosis through enhanced ROS production. DCA and quercetin reduced tumor growth and enhanced survival in immune-competent mice, correlating with decre...
Source: Cancers - Category: Cancer & Oncology Authors: Yongxian Zhuang Joseph D. Coppock Allison B. Haugrud John H. Lee Shanta M. Messerli W. Keith Miskimins Tags: Article Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Epithelial Cancer | Flavonoids | Fruit | Head and Neck Cancer | HNSCC | Oropharyngeal Cancer | Skin Cancer | Squamous Cell Carcinoma | Vegetables